Micro-fluidic chip for inhalation sprayer

Abstract

A silicon chip 1 and a glass sheet 2 form a semi-closed inner cavity through anodic bonding, the micro-fluidic chip comprises an inlet end 3 and an outlet end 4, the outlet end comprises a left outlet 41 and a right outlet 42, and the left outlet and the right outlet are in axial symmetry relative to the central axis X of the micro-fluidic chip. The axis Y of the left outlet, the axis Y'of the right outlet and the central axis X intersect at a point A. The outlet end comprises a cutting starting line U0, the vertical distance between the point A and the cutting starting line U0 is L, the outlet end further comprises a cutting buffer line U1, and fluid in the micro-fluidic chip is sprayed out from the cutting buffer line U1. The vertical distance from the cutting buffer line U1 to the cutting start line U0 is a cutting buffer distance L ', and L' is less than or equal to L, so that the fluid is ensured to collide and spray outside the chip, the cutting buffer distance protects the integrity of the outlet end when the micro-fluidic chip is cut, the overall quality and yield of the micro-fluidic chip are improved, and the cost is reduced.

Description

TECHNICAL FIELD

[0001] The utility model relates to a kind of microfluidic chip, especially a microfluidic chip in nebulizer for inhalation administration, belong to medical instrument technical field. BACKGROUND

[0002] Microfluidics is the sample preparation, reaction, separation, detection and other basic operation units of biological, chemical, medical analysis process are integrated to a micron scale chip, and the whole analysis process is automatically completed.Microfluidic chip is the main platform of microfluidic technology realization.The device features are mainly that the effective structure (channel, reaction chamber and other certain functional components) of its fluid containing is at least micron scale in one latitude.Due to micron scale structure, fluid shows and generates special performance different from macro scale in it.Due to its huge potential in biology, chemistry, medicine and other fields, it has developed into a new research field of biology, chemistry, medicine, fluid, electronics, materials, mechanics and other disciplines.

[0003] Hand-held inhalation nebulizer produced by Boehringer Ingelheim company in Germany It is a device used by patient for long time without supervision.In some cases, such as asthma patient, the width and angle formed by nebulization and the angle between nebulizer and human throat when using nebulizer is a crucial index for evaluating the amount of final drug deposited in lung.CN1809424A discloses a microstructure high-pressure nozzle with built-in filtering function and its manufacturing method.The high-pressure nozzle is obtained by silicon wafer photolithography+etching, then glass wafer anodic bonding and individual cutting process (hereinafter referred to as "microfluidic chip").As one of the components of nebulizer, the width and angle formed by nebulization of nebulizer is mostly determined by microfluidic chip, so the quality of microfluidic chip directly determines the quality of nebulizer in some level.

[0004] Specifically, it has cutting starting line (refer to U0 in the attached Fig. 3-6 and cuts at the place, and has no cutting buffer line (refer to U1 in the attached Fig. 3-6 and spray guide line (refer to T and T' in the attached Fig. 3-6 Therefore, in the cutting process of microfluidic chip, once fragmentation occurs at cutting starting line, it will cause the incompleteness of chip spray outlet, thereby affecting the nebulization effect.Usually, such fragmented microfluidic chip will be rejected in sampling detection of factory products, which means that it has relatively high product failure rate.In summary, the shortcomings are that firstly, low product yield will lead to high total production cost of product, and secondly, high failure rate will increase sampling inspection frequency and sampling quantity when product is shipped, thereby further increasing the production cost of product. Utility model content

[0005] The utility model discloses to overcome the above-mentioned shortcoming in prior art, improve the overall quality and yield of micro fluidic chip, reduce production cost, and can guarantee that micro fluidic chip is assembled to inhalation atomizer and can form the expected spray angle, spray area and particle size.

[0006] Preferably, the micro fluidic chip of the utility model is realized mainly through the following structure.

[0007] A micro fluidic chip is composed of a silicon wafer and a glass wafer by anode bonding to form a semi-closed internal cavity, comprising an inlet end and an outlet end, the outlet end comprises a left outlet and a right outlet, the left outlet and the right outlet are axisymmetric relative to the central axis X of the micro fluidic chip, the axis Y of the left outlet and the axis Y' of the right outlet meet the central axis X at point A, the outlet end comprises a cutting starting line U0, the vertical distance from point A to the cutting starting line U0 is L, the outlet end further comprises a cutting buffer line U1, the fluid in the micro fluidic chip is sprayed from the cutting buffer line U1, the vertical distance from the cutting buffer line U1 to the cutting starting line U0 is a cutting buffer distance L', L'≤L.

[0008] The micro fluidic chip of the utility model controls L'≤L, so as to guarantee that the fluid in the micro fluidic chip is sprayed from the left outlet and the right outlet and then collides and sprays outside the micro fluidic chip, and the cutting buffer distance can protect the integrity of the outlet end when the micro fluidic chip is cut, and improve the overall quality of the micro fluidic chip.

[0009] In some preferred embodiments, the micro fluidic chip of the utility model, L' is about 0.1 microns to 5 microns. In other preferred embodiments, L' is about 0.5 microns to 1.5 microns. In still other preferred embodiments, L' is about 1.5 microns.

[0010] In some preferred embodiments, the micro fluidic chip of the utility model, the included angle between Y and Y' ranges from 80° to 120°. In other preferred embodiments, the included angle between Y and Y' ranges from 85° to 95°.

[0011] In some preferred embodiments, when the included angle between Y and Y' is 90°, L is about 25 microns.

[0012] In some preferred embodiments, the micro fluidic chip of the utility model, the outlet end further comprises spray guide lines on both sides, the left spray guide line T and the right spray guide line T' are axisymmetric relative to the central axis X.

[0013] In some preferred embodiments, the angle a between the spray guide line T / T' and the axis Y / Y' is in the range of 0° to 135°. In other preferred embodiments, the angle a between the spray guide line T / T' and the axis Y / Y' is in the range of 0° to 90°. In still other preferred embodiments, the angle a between the spray guide line T / T' and the axis Y / Y' is in the range of 45° to 90°.

[0014] The utility model also provides an inhalation sprayer containing the microfluidic chip of any one of the above, and the spray outlet of the inhalation sprayer is the outlet end of the microfluidic chip.

[0015] Technical effects: the utility model adds the cutting buffer line (U1) and the spray guide line (T, T') in the prior art microfluidic chip, cuts directly at the cutting buffer line in the product production process, and it is found that the spray effect is not affected under the premise of improving the yield of products.

[0016] Specifically:

[0017] 1. The spray yield of the microfluidic chip is improved from 70% to 95%.

[0018] 2. The spray effect data of the microfluidic chip is basically consistent with the spray effect data of the prior art microfluidic chip. BRIEF DESCRIPTION OF DRAWINGS

[0019] Fig. 1-1 And Fig. 1-3 is the overall structure schematic diagram of the microfluidic chip, Fig. 1-2 is Fig. 1-1 the local enlarged view of part A in the figure, Fig. 1-4 is Fig. 1-3 the local enlarged view of part B in the figure.

[0020] Fig. 2 is the plate arrangement schematic diagram (wafer layout) of multiple microfluidic chips;

[0021] Fig. 3 is the outlet end structure schematic diagram when the angle between the spray guide line and the outlet channel center line of the microfluidic chip is 0°;

[0022] Fig. 4 is the outlet end structure schematic diagram when the angle between the spray guide line and the outlet channel center line of the microfluidic chip is 45°;

[0023] Fig. 5 is the outlet end structure schematic diagram when the angle between the spray guide line and the outlet channel center line of the microfluidic chip is 90°;

[0024] Fig. 6 is the schematic diagram of the outlet end structure of the micro-fluidic chip when the included angle between the spray guide line and the center line of the outlet channel is 135°;

[0025] Fig. 7 is inhalation nebulizer Fig. 4 is the schematic diagram of the angle of the spray formed when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the overall spray angle can reach 21.5°;

[0026] Fig. 8 is inhalation nebulizer Fig. 4 is the schematic diagram of the cross section at a distance of 3 cm from the nozzle when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the spray cross section at 3 cm can reach 199.6 mm 2 ;

[0027] Fig. 9 is inhalation nebulizer Fig. 4 is the schematic diagram of the cross section at a distance of 6 cm from the nozzle when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the spray cross section at 6 cm can reach 409.2 mm 2 ;

[0028] Fig. 10 is inhalation nebulizer Fig. 5 is the schematic diagram of the angle of the spray formed when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the overall spray angle can reach 21.15°;

[0029] Fig. 11 is inhalation nebulizer Fig. 5 is the schematic diagram of the cross section at a distance of 3 cm from the nozzle when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the spray cross section at 3 cm can reach 196.3 mm 2 ;

[0030] Fig. 12 is inhalation nebulizer Fig. 5 is the schematic diagram of the cross section at a distance of 6 cm from the nozzle when the micro-fluidic chip with the structure is sprayed, and it can be seen from the diagram that the spray cross section at 6 cm can reach 400.0 mm 2 .

[0031] Explanation of reference signs

[0032] 1 silicon wafer 2 glass wafer 3 inlet end 4 outlet end

[0033] 5 anode bonding wire 41 left outlet 42 right outlet

[0034] X center line of the chip Y, Y' center line of the outlet channel A collision point of the spray U0 cutting start line

[0035] U1 cutting buffer line L vertical distance from the collision point A of the spray to the cutting start line

[0036] L' cutting buffer distance T, T' spray guide line α spray guide angle DETAILED DESCRIPTION

[0037] In order to make the purpose, technical scheme and advantages of the utility model more clear and apparent, the specific embodiments of the microfluidic chip for the sprayer of the utility model will be further described below in conjunction with the drawings. It should be understood that: the embodiments of the utility model are only given for illustrating the utility model, and are not a limitation on the utility model, and the simple improvements of the utility model under the premise of the technical scheme of the utility model all belong to the protection scope of the utility model. In addition, in the following description, the description of the known structure and technology is omitted to avoid unnecessary confusion of the concept of the utility model.

[0038] The structural schematic diagrams of some specific embodiments of the utility model are shown in the drawings. These drawings are not drawn to scale, and for the purpose of clarity, some details can be enlarged or omitted. The various regions, shapes and their relative size and position relationship shown in the drawings are only exemplary, and are not a limitation on the specific parameter size or position relationship of the utility model.

[0039] In conjunction with Fig. 1-1 , 1-2 , 1-3, 1-4, a microfluidic chip is composed of a silicon wafer 1 and a glass wafer 2 by anode bonding to form a semi-closed internal cavity, including an inlet end 3 and an outlet end 4, and the outlet end includes a left outlet 41 and a right outlet 42. In conjunction with Fig. 3-6 , the left outlet 41 and the right outlet 42 are axisymmetric with respect to the central axis X of the microfluidic chip, and the axis Y of the left outlet 41 and the axis Y' of the right outlet 42 intersect at point A with the central axis X, so as to ensure that when the microfluidic chip is assembled to the inhalation sprayer for use, the fluid enters the internal cavity channel of the chip from the inlet end of the microfluidic chip, and two liquid jets are generated at the outlet to converge and collide at a set angle to generate aerosol. The outlet end includes a cutting start line U0, and the vertical distance from point A to the cutting start line U0 is L, and the outlet end further includes a cutting buffer line U1, the fluid in the microfluidic chip is sprayed from the cutting buffer line U1, and the vertical distance from the cutting buffer line U1 to the cutting start line U0 is the cutting buffer distance L', L'≤L.

[0040] In conjunction with Fig. 3-6As shown, L' is about 0.1 μm to 5 μm. Preferably, L' is about 0.5 μm to 1.5 μm. More preferably, L' is about 1.5 μm.

[0041] Combination Fig. 3-6 As shown, the angle between Y and Y' is in the range of 80° to 120°. Preferably, the angle between Y and Y' is in the range of 85° to 95°. Based on this angle, the shape of the aerosol spray, including the angle and width, can be defined. When the angle between Y and Y' is 90°, L is about 25 microns.

[0042] Combination Fig. 3-6 As shown, the outlet end further comprises two spray guide lines on both sides, a left spray guide line T and a right spray guide line T' which are axially symmetrical relative to the central axis X.

[0043] The angle between the spray guide line T (or T') and the axial line Y (or Y') is in the range of 0° to 135°.

[0044] Fig. 3 In the middle, the spray guide angle α of the microfluidic chip is 0°.

[0045] Fig. 4 In the middle, the spray guide angle α of the microfluidic chip is 45°.

[0046] Fig. 5 In the middle, the spray guide angle α of the microfluidic chip is 90°.

[0047] Fig. 6 In the middle, the spray guide angle α of the microfluidic chip is 135°.

[0048] As Fig. 3-6 As shown in the middle, the cutting buffer distance L' limits the cutting position outside the cutting starting line U0, without hindering the ejection of the drug solution from the left and right outlets of the microfluidic chip and the collision of the spray at the collision point A outside the chip.

[0049] In some embodiments, the microfluidic chip of the present application can be loaded into a suitable inhalation sprayer, and the spray outlet of the inhalation sprayer is the outlet end 4 of the microfluidic chip.

[0050] Spray effect test

[0051] In the following spray effect test, the inhalation sprayer used in the present application is the Inhaler produced by Boehringer Ingelheim Company in Germany. The microfluidic chip of the prior art refers to The original microfluidic chip of the inhaler. The spray effect diagram is shown in the attached Fig. 7-12 .

[0052] Specific operation method:

[0053] The test instruments used in test items 1-3 are as follows:

[0054] Instrument Manufacturer Model Spray Pattern and Spray Morphology Analyzer Proveris Scientific, USA Spray VIEW

[0055] The weight sensor calibration of the pressing device and the operation calibration of the pressing device are sequentially performed according to the standard operation procedures of the instrument, and the test is performed after the calibration is passed.

[0056] The Tiotropium Br Spr Method 3 under the Method item is selected to perform the spray mode test; the Tiotropium Br Spr Method 6 under the Method item is selected to perform the 3cm spray mode test; and the Tiotropium Br Spr Method 5 under the Method item is selected to perform the 6cm spray mode test.

[0057] The test instruments used in test item 4 are as follows:

[0058] Instrument Manufacturer Model Particle Size Tester Sympatec GmbH, Germany HELOS & SPRAYER

[0059] The device with the microfluidic chip is inserted into the instrument, the relative humidity and flow rate of the instrument system are balanced, and then the particle size data of the completed determination is read.

[0060] The test results are shown in Table 1.

[0061] Table 1: Spray effect test results

[0062]

[0063] According to the results of Examples 1 and 2 in Table 1, when the α angle in the microfluidic chip of the utility model is about 45° (Example 1) or about 90° (Example 2), the spray effect of the sprayer using the microfluidic chip is basically the same as that of the existing microfluidic chip (Comparative Example 1, Boehringer Ingelheim (Germany) produced Inhaler and its original microfluidic chip). That is, when the α angle is 45°-90°, a good spray effect can be achieved. Accordingly, it can be inferred that when the α angle is 0-135°, a good spray effect can also be achieved.

[0064] Spray yield test

[0065] Referring to the layout shown in Fig. 2 After all the manufacturing processes are completed, there are about 2000 microfluidic chips on the whole wafer, 200 of which are randomly sampled on the surface of the wafer and subjected to the above spray test, and the results show that the yield reaches 95%.

Claims

1. A microfluidic chip, which is composed of a silicon wafer (1) and a glass wafer (2) by anodic bonding to form a semi-closed internal cavity, comprising an inlet end (3) and an outlet end (4), the outlet end comprising a left outlet (41) and a right outlet (42), the left outlet (41) and the right outlet (42) being axisymmetric with respect to the central axis X of the microfluidic chip, the axis of the left outlet Y and the axis of the right outlet Y' intersecting the central axis X at a point A, the outlet end comprising a cutting starting line U0, the vertical distance from the point A to the cutting starting line U0 being L, characterized in that, The outlet end further comprises a cutting buffer line U1, from which the fluid in the microfluidic chip is ejected, and the vertical distance between the cutting buffer line U1 and a cutting start line U0 is a cutting buffer distance L', L'≤L.

2. The microfluidic chip of claim 1, wherein, L' is 0.1 μm to 5 μm.

3. The microfluidic chip of claim 1, wherein, L' is 0.5 μm to 1.5 μm.

4. The microfluidic chip of claim 1, wherein, L' is 1.5 μm.

5. The microfluidic chip of claim 1, wherein, The included angle between Y and Y' ranges from 80° to 120°.

6. The microfluidic chip of claim 1, wherein, The included angle between Y and Y' ranges from 85° to 95°.

7. The microfluidic chip of claim 1, wherein, The outlet end further comprises two-sided spray guide lines, the left spray guide line T and the right spray guide line T' being axisymmetric relative to the central axis X.

8. The microfluidic chip of claim 7, wherein, The included angle α between the spray guide line and the axis center line ranges from 0° to 135°.

9. The microfluidic chip of claim 7, wherein, The included angle α between the spray guide line and the axis center line ranges from 0° to 90°.

10. The microfluidic chip of claim 7, wherein, The included angle α between the spray guide line and the axis center line ranges from 45° to 90°.

Images